Association between surfactant protein B + 1580 polymorphism and the risk of respiratory failure in adults with community-acquired pneumonia

Crit Care Med. 2004 May;32(5):1115-9. doi: 10.1097/01.ccm.0000124872.55243.5a.

Abstract

Objective: Pulmonary surfactant protein (SP)-B plays a vital role in the formation and function of surfactant in the lung. A genetic polymorphism (SP-B + 1580) is postulated to result in diminished activity of SP-B. The objective was to determine whether the SP-B + 1580 CC genotype is associated with an increased risk of respiratory failure and ARDS in adults with community-acquired pneumonia.

Design: Prospective cohort of adults diagnosed with community-acquired pneumonia.

Setting: Hospital system.

Patients: We enrolled 402 adults > or = 18 yrs of age with community-acquired pneumonia; 158 were white, 243 were African American, and one was Asian.

Interventions: Genotypic analysis was performed on DNA isolated from whole blood using polymerase chain reaction amplification and DdeI restriction enzyme digestion.

Measurements and main results: We recorded the requirement for mechanical ventilation, the presence of acute respiratory distress syndrome (ARDS) or septic shock, and mortality. Sixty-three patients required mechanical ventilation, 12 patients developed ARDS, and 35 patients developed septic shock. Genotypic frequencies at the SP-B + 1580 site were T/T 183 of 402 (0.45), T/C 160 of 402 (0.40), and C/C 59 of 402 (0.15). Of the 59 patients who were C/C at the SP-B + 1580 site, 21 (0.356) required mechanical ventilation, compared with 26 of 160 patients (0.163) who were T/C and 16 of 183 (0.087) patients who were T/T (p < .001). ARDS developed in five of 59 (0.085) patients with the C/C genotype, compared with six of 160 (.038) patients with T/C and one of 183 patients with T/T (0.005, p < .009). Septic shock occurred in 12 of 59 (0.203) patients with the C/C genotype, compared with 13 of 160 (0.081) patients with T/C and ten of 183 (0.055) patients with T/T (p < .001). Mortality rate was not different between the three genotypes.

Conclusion: Carriage of the C allele at the SP-B + 1580 site is associated with ARDS, septic shock, and the need for mechanical ventilation in adults with community-acquired pneumonia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cause of Death
  • Chromosomes, Human, Pair 2 / genetics
  • Community-Acquired Infections / complications*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Hospital Mortality
  • Humans
  • Male
  • Middle Aged
  • Pneumonia / complications*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics*
  • Prospective Studies
  • Pulmonary Surfactant-Associated Protein B / genetics*
  • Pulmonary Surfactant-Associated Protein B / physiology
  • Respiration, Artificial / statistics & numerical data
  • Respiratory Distress Syndrome / etiology
  • Respiratory Distress Syndrome / mortality
  • Respiratory Distress Syndrome / therapy
  • Respiratory Insufficiency / etiology*
  • Respiratory Insufficiency / mortality
  • Respiratory Insufficiency / therapy
  • Restriction Mapping
  • Risk Factors
  • Shock, Septic / etiology
  • Shock, Septic / mortality
  • Shock, Septic / therapy
  • Tennessee / epidemiology

Substances

  • Pulmonary Surfactant-Associated Protein B